Suitability of transbronchial brushing cytology specimens for next‐generation sequencing in peripheral lung cancer

Furuya, Naoki; Matsumoto, Shingo; Kakinuma, Kazutaka; Morikawa, Kei; Inoue, Tatsuya; Saji, Hisashi; Goto, Kōichi; Mineshita, Masamichi

doi:10.1111/cas.14714

Cited by 22 publications

(33 citation statements)

References 20 publications

(41 reference statements)

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“…Currently, patients with SqCC are treated with various anticancer drugs, such as molecularly targeted drugs, immune checkpoint inhibitors, cytotoxic chemotherapy, and combination therapies of these drugs. Ninety-seven percent of cases resistant to chemotherapy were attributable to smoking 3 and, recently, next-generation sequencing has been used to easily detect some oncogenic driver mutations from small biopsy samples in clinical practice 4 . However, most cases of oncogenic-driven lung cancer are non-squamous NSCLC.…”

Section: Introductionmentioning

confidence: 99%

Protein co-expression network-based profiles revealed from laser-microdissected cancerous cells of lung squamous-cell carcinomas

Nishimura

Fujii

Nakamura

et al. 2021

Sci Rep

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No therapeutic targets have been identified for lung squamous cell cancer (SqCC) which is the second most prevalent lung cancer because its molecular profiles remain unclear. This study aimed to unveil disease-related protein networks by proteomic and bioinformatic assessment of laser-microdissected cancerous cells from seven SqCCs compared with eight representative lung adenocarcinomas. We identified three network modules significant to lung SqCC using weighted gene co-expression network analysis. One module was intrinsically annotated to keratinization and cell proliferation of SqCC, accompanied by hypoxia-induced aerobic glycolysis, in which key regulators were activated (HIF1A, ROCK2, EFNA1-5) and highly suppressed (KMT2D). The other two modules were significant for translational initiation, nonsense-mediated mRNA decay, inhibited cell death, and interestingly, eIF2 signaling, in which key regulators, MYC and MLXIPL, were highly activated. Another key regulator LARP1, the master regulator in cap-dependent translation, was highly suppressed although upregulations were observed for hub proteins including EIF3F and LARP1 targeted ribosomal proteins, among which PS25 is the key ribosomal protein in IRES-dependent translation. Our results suggest an underlying progression mechanism largely caused by switching to the cap-independent, IRES-dependent translation of mRNA subsets encoding oncogenic proteins. Our findings may help to develop therapeutic strategies to improve patient outcomes.

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Section: Introductionmentioning

confidence: 99%

Protein co-expression network-based profiles revealed from laser-microdissected cancerous cells of lung squamous-cell carcinomas

Nishimura

Fujii

Nakamura

et al. 2021

Sci Rep

Self Cite

View full text Add to dashboard Cite

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“…In an article 1 titled “Suitability of transbronchial brushing cytology specimens for next‐generation sequencing in peripheral lung cancer” by Naoki Furuya, Shingo Matsumoto, Kazutaka Kakinuma, Kei Morikawa, Takeo Inoue, Hisashi Saji, Koichi Goto, Masamichi Mineshita, the authors would like to correct the unit “mL” to “μL” in the Results section, Figure 2, Tables 2 and 3.…”

Section: Figurementioning

confidence: 99%

Correction

2021

Cancer Science

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“…During the enrollment and follow-up period of this cohort, four genetic screens of driver mutations, including EGFR and BRAF mutations and ALK and ROS1 fusions, had been approved and were commercially available for advanced NSCLC in Japan. Other genetic aberrations, such as KRAS mutations, were screened in the LC-SCRUM-Asia (formerly LC-SCRUM-Japan) consortium [ 13 ], which employed an amplicon-based next-generation sequencing (NGS) panel, Oncomine Comprehensive Assay (Thermo Fisher Scientific, Waltham, MA). Tumor responses to nivolumab monotherapy were assessed by the investigators according to RECIST (Response Evaluation Criteria in Solid Tumors) version 1.1.…”

Section: Methodsmentioning

confidence: 99%

Gene expression signatures as candidate biomarkers of response to PD-1 blockade in non-small cell lung cancers

et al. 2021

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Although anti-PD-1/PD-L1 monotherapy has achieved clinical success in non-small cell lung cancer (NSCLC), definitive predictive biomarkers remain to be elucidated. In this study, we performed whole-transcriptome sequencing of pretreatment tumor tissue samples and pretreatment and on-treatment whole blood samples (WB) samples obtained from a clinically annotated cohort of NSCLC patients (n = 40) treated with nivolumab (anti-PD-1) monotherapy. Using a single-sample gene set enrichment scoring method, we found that the tumors of responders with lung adenocarcinoma (LUAD, n = 20) are inherently immunogenic to promote antitumor immunity, whereas those with lung squamous cell carcinoma (LUSC, n = 18) have a less immunosuppressive tumor microenvironment. These findings suggested that nivolumab may function as a molecular targeted agent in LUAD and as an immunomodulating agent in LUSC. In addition, our study explains why the reliability of PD-L1 expression on tumor cells as a predictive biomarker for the response to nivolumab monotherapy is quite different between LUAD and LUSC.

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Suitability of transbronchial brushing cytology specimens for next‐generation sequencing in peripheral lung cancer

Abstract: This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

Cited by 22 publications

References 20 publications

Protein co-expression network-based profiles revealed from laser-microdissected cancerous cells of lung squamous-cell carcinomas

Protein co-expression network-based profiles revealed from laser-microdissected cancerous cells of lung squamous-cell carcinomas

Correction

Gene expression signatures as candidate biomarkers of response to PD-1 blockade in non-small cell lung cancers

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